Copeptin revealed to be a valuable and reliable diagnostic biomarker in the differential diagnosis of Diabetes insipidus

HENNIGSDORF, GERMANY – February 03, 2020 – The winner of the EJE Award 2019 is Mirjam Christ-Crain, professor of Endocrinology, Diabetes, and Metabolism at the University of Basel, Switzerland (interview). Results from her recent research show that using Copeptin measurement has the potential to replace the so-called “classic” but unspecific water deprivation test. “The diagnostic accuracy using Copeptin is 96.5 percent while it is only 76.6 percent in the water deprivation test which is significantly lower,” Mirjam Christ-Crain said in her ECE lecture, the article is published in the European Journal of Endocrinology (1).

Diabetes insipidus (DI) is a rare and incurable disorder that affects a person’s ability to regulate body fluid balance. Available treatments can relieve thirst and decrease urine output. Nonetheless, current diagnostic practice is challenging and vulnerable to false results, especially in patients with primary polydipsia. As treatment strategies for the different forms of DI vary and applying the wrong therapy can be dangerous, a reliable differential diagnosis is crucial.

A study published in the New England Journal of Medicine in 2018 (2) concluded that the measurement of Copeptin had a greater diagnostic accuracy than the classical water deprivation test. The use of the Copeptin assay has the advantage to reduce the duration of water deprivation testing from 17 hours to less than 2 hours and the test can be performed on an outpatient basis instead during a hospital stay. Accordingly, this lowers the burden of testing for the patient substantially. For further simplification of the diagnostic algorithm, a new method using arginine as a stimulant has been introduced by Prof. Christ-Crain and was recently published in Lancet (3). Authors conclude ”… we propose arginine stimulation as a simplified, novel, and safe diagnostic approach to Diabetes insipidus.”

In Europe, the B·R·A·H·M·S Copeptin proAVP KRYPTOR test is indicated to be used in conjunction with additional clinical data as an aid in assessing the differential diagnosis of patients with water balance disorders, e.g. polyuria-polydipsia syndrome or syndrome of inappropriate ADH secretion (SIADH). The test is further indicated as an aid to be used in conjunction with cardiac troponin and the clinical evaluation in ruling out acute myocardial infarction in patients presenting with chest pain or equivalent symptoms of cardiac origin. The B·R·A·H·M·S CT-proAVP LIA test is indicated to be useful in any diseases related to a disturbance of AVP release and/or electrolyte disturbances. The main indications for CT-proAVP determination are therefore the differential diagnosis of polyuria-polydipsia syndrome and differential diagnosis of hyponatremia (e.g. SIADH).

Both Copeptin assay formats were used in Prof. Christ-Crain’s studies on vasopressin-dependent disorders.

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About Copeptin

Copeptin, part of the vasopressin prohormone, is a marker of the individual hemodynamic stress response. Arginine vasopressin (AVP) is a key hormone in the human body. Despite the clinical relevance of AVP in maintaining fluid balance and vascular tone, measurement of mature AVP is difficult and subject to pre-analytical errors. Copeptin, a 39-amino acid glycopeptide that comprises the C-terminal part of the AVP precursor (CT-proAVP), has been found to be a stable and sensitive surrogate marker for AVP, analogous to C-peptide for insulin. Copeptin measurement has been shown to be useful in various clinical indications, circulating Copeptin levels rise to peak values rapidly and then decline over the next hours. The pre-pro-vasopressin precursor is synthesized and processed into its three components – AVP, Neurophysin II, and Copeptin – within the hypothalamus; afterward, these products are transported along the neuronal axons in the granules of the posterior hypophysis (pituitary gland), where they are stored and released under the appropriate stimulus. The immunoassays Thermo Scientific B·R·A·H·M·S Copeptin proAVP KRYPTOR and Thermo Scientific B·R·A·H·M·S CT-proAVP LIA are part of a series of biomarker assays which can be used in cardiology and endocrinology.

About Thermo Fisher Scientific

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  1. Mirjam Christ-Crain. European Journal of Endocrinology (2019) 180, R11–R21
  2. W. Fenske, J. Refardt, I. Chifu, I. Schnyder, B. Winzeler, J. Drummond, A. Ribeiro‑Oliveira, Jr., T. Drescher, S. Bilz, D.R. Vogt, U. Malzahn, M. Kroiss, E. Christ, C. Henzen, S. Fischli, A. Tönjes, B. Mueller, J. Schopohl, J. Flitsch, G. Brabant, M. Fassnacht, and M. Christ‑Crain. A Copeptin-Based Approach in the Diagnosis of Diabetes Insipidus. N Engl J Med 2018;379:428-39.
  3. Bettina Winzeler, Nicole Cesana-Nigro, Julie Refardt, Deborah R Vogt, Cornelia Imber, Benedict Morin, Milica Popovic, Michelle Steinmetz, Clara O Sailer, Gabor Szinnai, Irina Chifu, Martin Fassnacht, Mirjam Christ-Crain. Arginine-stimulated copeptin measurements in the differential diagnosis of diabetes insipidus: a prospective diagnostic study. LANCET 2019

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